Clinical implications of elevated serum interleukin-6 in IgG4-related disease.

INTRODUCTION: Some patients with IgG4-related disease (IgG4-RD) exhibit elevated serum interleukin (IL)-6 with excessive inflammatory reactions or with repeating relapse. To date few reports pertaining to clinical implications of elevated serum IL-6 in IgG4-RD patients have been published. The aims of the current retrospective study were to investigate the clinical implications of elevated serum IL-6 in IgG4-RD patients, and to examine whether IL-6 can predict the activity and/or relapse of the disease. MATERIALS AND METHODS: We examined the clinical picture at the onset of 43 patients who were diagnosed with IgG4-RD in our hospital and were able to measure serum IL-6 before steroid treatment. RESULTS: The median level of serum IL-6 was 2.2 pg/mL. There was a significant correlation between IL-6 and C-reactive protein (CRP) level (r = 0.397, p = 0.008), hemoglobin level (r = -0.390, p = 0.010) and albumin level (r = -0.556, p < 0.001). When 43 patients were divided into two groups by using a cut-off IL-6 of 4 pg/mL, the high IL-6 group showed higher age, lower albumin, higher CRP and higher aspartate aminotransferase (AST) (age p = 0.014, albumin p = 0.006, CRP p <0.001, AST p = 0.009). Hepatic swelling and splenomegaly were significantly more prevalent in the high IL-6 group than it was in the low IL-6 group (liver p < 0.001, spleen p = 0.020). Biliary tract involvement tended to admit more in the high IL-6 group (p = 0.060). CONCLUSION: Serum IL-6 level at the onset of IgG4-RD may be significantly correlated with clinical inflammatory parameters and it may also be associated with involvement of the bile duct, liver, and spleen.

Correction to: Basophils activated via TLR signaling may contribute to pathophysiology of type 1 autoimmune pancreatitis.

In the original publication of this article, the Table 2 was published incorrectly.

Basophils activated via TLR signaling may contribute to pathophysiology of type 1 autoimmune pancreatitis.

BACKGROUND: Pathophysiology of type 1 autoimmune pancreatitis (AIP) is still unclear. We previously reported that M2 macrophages might play an important role in type 1 AIP. Recently, it has been reported that basophils regulate differentiation to M2 macrophages. In this study, we investigated basophils from the pancreatic tissue and peripheral blood of individuals with type 1 AIP. METHODS: By using immunohistochemistry, we investigated basophils in pancreatic tissue from 13 patients with type 1 AIP and examined expression of toll-like receptors (TLRs) by these cells. Additionally, we obtained peripheral blood samples from 27 healthy subjects, 40 patients with type 1 AIP, 8 patients with alcoholic chronic pancreatitis, 10 patients with bronchial asthma, and 10 patients with atopic dermatitis, and analyzed activation of basophils by stimulating them with ligands of TLR1-9. We also compared TLR expression in basophils from the tissue and blood samples. RESULTS: Basophils were detected in pancreatic tissues from 10 of 13 patients with type 1 AIP. Flow cytometric analysis revealed that the ratios of basophils activated by TLR4 stimulation in type 1 AIP (9.875 ± 1.148%) and atopic dermatitis (11.768 ± 1.899%) were significantly higher than those in healthy subjects (5.051 ± 0.730%; P < 0.05). Levels of basophils activated by TLR2 stimulation were higher in seven type 1 AIP cases. Furthermore, stimulation of TLR2 and/or TLR4, which were expressed by basophils in pancreas, activated basophils in peripheral blood. CONCLUSIONS: Basophils activated via TLR signaling may play an important role in the pathophysiology of type 1 AIP.

Sclerosing Esophagitis with IgG4-positive Plasma Cell Infiltration.

The patient was a 76-year-old woman who had noticed slight difficulty in swallowing in the 3 years prior to this presentation. Her dysphagia progressed while she was hospitalized following cervical cancer surgery. Esophagogastroduodenoscopy and an esophagram showed circumferential erosion and a stricture of the thoracic esophagus. Esophageal resection was performed; the resected specimens showed a stricture and wall thickening. Histologically, transmural hyperplasia, which consisted of inflammatory granulation tissue with the abundant infiltration of IgG4-positive plasma cells and lymphocytes, was observed. The patient was diagnosed with probable IgG4-related disease. IgG4-related esophageal disease presenting as esophageal lesions alone is a very rare condition.

Morphological and immunohistochemical comparison of intrapancreatic nerves between chronic pancreatitis and type 1 autoimmune pancreatitis.

OBJECTIVES: The abdominal pain associated with chronic pancreatitis (CP) may be related to the increased number and size of intrapancreatic nerves. On the other hand, patients with type 1 autoimmune pancreatitis (AIP) rarely suffer from the pain syndrome, and there are no previous studies concerning the histopathological findings of intrapancreatic nerves in patients with type 1 AIP. The current study is aimed at investigating the differences in the histopathological and immunohistochemical findings of intrapancreatic nerves in patients with CP and type 1 AIP. METHODS: Neuroanatomical differences between CP and type 1 AIP were assessed by immunostaining with a pan-neuronal marker, protein gene product 9.5 (PGP9.5). The number (neural density) and area (neural hypertrophy) of PGP9.5-immunopositive nerves were quantitatively analyzed. Furthermore, the expression of nerve growth factor (NGF), and a high affinity receptor for NGF, tyrosine kinase receptor A (TrkA), was assessed by immunohistochemistry. RESULTS: Both neural density and hypertrophy were significantly greater in pancreatic tissue samples from patients with CP than those with normal pancreas or type 1 AIP. NGF expression was stronger in type 1 AIP than in CP, whereas TrkA expression in type 1 AIP was poorer than in CP. CONCLUSIONS: Although CP and type 1 AIP are both characterized by the presence of sustained pancreatic inflammation, they are different in terms of the density and hypertrophy of intrapancreatic nerve fibers. It is possible that this may be related to the difference in the activity of the NGF/TrkA-pathway between the two types of pancreatitis.

IgG4-related Disease Involving Multiple Organs with Elevated Serum Interleukin-6 Levels.

A 63-year-old woman presented to our hospital with elevated levels of serum IgG4, marked wall thickening of the gallbladder, hepatomegaly, and abdominal lymphadenopathy. She experienced a recurrent fever and leg edema. Her laboratory data demonstrated anemia, hypoalbuminemia, and elevated serum levels of interleukin-6 and C-reactive protein. The patient was eventually diagnosed with IgG4-related disease according to the comprehensive diagnostic criteria, although the patient exhibited common clinical manifestations of multicentric Castleman disease such as a fever, anemia, lymphadenopathy, and elevated levels of serum interleukin-6 and C-reactive protein. This case report highlights the difficulties in differentiating between these two diseases.

Diagnostic yield of double-balloon enteroscopy with intestinal juice analysis for intestinal strongyloidiasis.

Strongyloidiasis is relatively common in tropical and subtropical areas. Most patients with Strongyloides stercoralis hyperinfection are immunocompromised, most commonly from corticosteroids or human T-cell lymphoma virus type 1 (HTLV-1) infection. We encountered a patient with HTLV-1 infection accompanied by paralytic ileus, in whom strongyloidiasis in the duodenum and jejunum was disclosed by esophagogastroduodenoscopy (EGD) and double-balloon enteroscopy (DBE). Until the age of 7 years, he lived on Amami-Oshima Island, Japan, where both S. stercoralis and HTLV-1 are endemic. EGD and peroral DBE disclosed white villi, edematous mucosa, and the disappearance of folds in the duodenum and jejunum. Biopsy specimens from the white villi in the duodenum and jejunum revealed S. stercoralis larvae. In both duodenal and jejunal juice, the rhabditiform larvae moved around. Because the larvae invade the lymph vessels, resulting in lymphangiectasia in edematous enteritis, the appearance of white villi may reflect villous atrophy/destruction and mucosal edema. Although our patient revealed no eosinophilia and negative stool specimens for parasites or ova, EGD and DBE with multiple biopsies and intestinal juice analysis are valuable diagnostic tools for strongyloidiasis.

Percutaneous microwave coagulation therapy for hepatocellular carcinoma: increased coagulation diameter using a new electrode and microwave generator.

We performed percutaneous microwave co-agulation therapy (PMCT) using a new microwave electrode and microwave generator to lessen the number of microwave electrode insertions for hepatocellular carcinoma (HCC) measuring 2 to 2.5 to or=5 mm on dynamic computed tomography. Necrosis of HCC and the non-cancerous area surrounding the tumor was obtained by a single needle insertion in 23 patients (tumor size: 2 to 2.5 to 2 to 2.5 to or=5 mm, we have not detected local recurrences. On the other hand, 4 of the 10 patients who could not obtain the treated margin of >or=5 mm, experienced a local recurrence. No fatal complications were observed. However, bile duct stricture was observed in 2 patients. The new microwave coagulation system can induce extensive necrosis with a small number of microwave electrode insertions. This system may enhance the efficacy of PMCT for HCC measuring <3.0 cm in diameter.